Personalized aortic valve prosthesis

ABSTRACT

A personalized prosthetic valve for implantation at a native valve treatment site includes a self-expanding mesh and a plurality of valve leaflets coupled to the mesh. The mesh may be delivered to the native valve in a collapsed configuration, and in an expanded configuration the mesh engages the native valve. The mesh in the expanded configuration is also personalized to match the treatment site, such that the outer mesh surface substantially matches the treatment site shape and size. The self-expanding mesh forms a central lumen configured to allow blood or other body fluids to pass therethrough. In the open configuration, blood passes through the prosthetic valve, and in the closed configuration, the plurality of leaflets are closer together and blood is prevented from flowing upstream through the prosthetic valve.

CROSS-REFERENCE TO RELATED APPLICATIONS

The present application is a non-provisional of, and claims the benefitof U.S. Provisional Patent Application No. 61/817,993 (Attorney DocketNo. 45045-704.101) filed May 1, 2013; the entire contents of which areincorporated herein by reference.

The present application is related to U.S. patent application Ser. No.13/663,160 (WSGR ref 22520-703.201) filed Oct. 29, 2012; the entirecontents of which are incorporated herein by reference.

BACKGROUND OF THE INVENTION Field of the Invention

The present application generally relates to medical devices andmethods. More particularly, the present invention relates to thefabrication and use of personalized medical prostheses that conform insize and/or shape to the anatomy of their intended locations in humanbody. More specifically, the present application relates to thestructure of the self expanding, anatomically conformal prosthesis as areplacement for the aortic valve of the human body.

Native valves in the human body can fail for a number of reasons.Traditional surgical methods have been used to repair these valves butthis often requires major surgery and a lengthy recovery period. Newerminimally invasive techniques are promising, but it can be difficult toaccurately deliver a prosthetic valve and anchoring the prosthesis mayalso be challenging. Furthermore, prosthetic valves also can developperivalvular leaks. Therefore, it would be desirable to provide improvedprosthetic valves that can be easily delivered, securely anchored, andthat do not leak. At least some of these objectives will be satisfied bythe exemplary embodiments disclosed below.

The terms ‘mesh’ and “frame” are used interchangeably in thisapplication to denote the prostheses which are being deployed in theaortic valve location in the aorta. Exemplary embodiments are directedat aortic valves, but this is not intended to be limiting and one ofskill in the art will appreciate that any number of valves may betreated using the prostheses disclosed herein, including but not limitedto other heart valves, venous valves, or other anatomical valvestructures.

SUMMARY OF THE INVENTION

The present application generally relates to the structure of the selfexpanding frame as a replacement for native valves such as the aorticvalve in the body. More specifically, the invention describes astructure of a conformal frame constructed for a specific aortic sinusanatomy. The frame has anatomically accurate placement of the ostia forthe coronary arteries in the aortic sinus which allows for access to thecoronary arteries for coronary interventions after implantation of theprosthetic valve, if needed. In addition, the frame has a membranedisposed on a portion thereof to protect against perivalvular leaks.

A main aspect of the present disclosure is to describe a structure and amethod the fabrication of a mesh which matches the anatomy of a givenpatient. The details of this are given in the full description of theaccompanying drawings.

In a first aspect of the present invention, a method for manufacturing apersonalized prosthetic valve comprises providing one or more images ofa native valve, creating a digital data set characterizing shape andsize of the native valve based on the one or more images, andtransforming the digital data set into machining instructions. Themethod also comprises forming a mandrel using the machininginstructions, wherein the mandrel has a shape that substantially matchesthe treatment site shape, applying a mesh to the mandrel, and heattreating the mesh while the mesh is disposed on the mandrel so that themesh is biased to return to a shape matching the shape of the treatmentsite thereby forming the personalized prosthetic valve. The personalizedprosthetic valve has a contracted configuration and an expandedconfiguration. In the contracted configuration, the prosthetic valve isadapted to be delivered to the native valve, and the prosthetic valve isbiased to return to the expanded configuration which substantiallymatches the shape of the native valve.

In another aspect of the present invention, a personalized prostheticvalve for implantation at a native valve treatment site comprises aself-expanding mesh having a collapsed configuration and an expandedconfiguration. The collapsed configuration is adapted to be delivered tothe native valve treatment site, and the expanded configuration isadapted to expand the personalized prosthetic valve into engagement withthe treatment site. The mesh in the expanded configuration ispersonalized to match the treatment site, and the mesh has an outersurface that substantially matches the treatment site shape and size inthe expanded configuration. The self-expanding mesh forms a centrallumen that is configured to allow blood or other body fluids to passtherethrough. The personalized prosthetic valve further comprises aplurality of valve leaflets coupled to the self-expanding mesh and hasan open configuration and a closed configuration. In the openconfiguration blood is free to pass through the prosthetic valve, and inthe closed configuration the plurality of leaflets are closer toward oneanother than in the open configuration, and blood is prevented fromflowing upstream through the prosthetic valve.

In another aspect of the present invention a personalized prostheticvalve for implantation at a native valve treatment site comprises aself-expanding mesh having a collapsed configuration and an expandedconfiguration. The collapsed configuration is adapted to be delivered tothe native valve treatment site, and the expanded configuration isadapted to expand the valve into engagement with the treatment site. Themesh in the expanded configuration is personalized to match thetreatment site, and the mesh has an outer surface that substantiallymatches the native valve treatment site shape and size in the expandedconfiguration. The self-expanding mesh forms a central lumen configuredto allow blood or other body fluids to pass therethrough, and the valvefurther comprises a plurality of valve leaflets coupled to theself-expanding mesh and that have an open configuration and a closedconfiguration. In the open configuration the blood or the other bodyfluids are free to pass through the valve, and in the closedconfiguration the plurality of leaflets are closer toward one anotherthan in the open configuration, and the blood or the other body fluidsare prevented from flowing upstream through the prosthetic valve.

The self-expanding mesh may comprise nitinol, or the mesh may compriseone or more filaments in a helical pattern. The self-expanding mesh maycomprise one or more filaments woven together to form overlappingregions with the one or more filaments overlapping one another at leastonce. The one or more filaments may be woven together to form a firstoverlapping region and a second overlapping region. The firstoverlapping region the filaments may overlap with one another a firstnumber of times, and in the second overlapping region the filaments mayoverlap with one another a second number of times different than thefirst number of times. The self-expanding mesh may comprise barbs orhooks adapted to engage tissue at the treatment site and anchor thepersonalized prosthesis. The plurality of overlapping filaments may formoverlapping regions, and the overlapping regions may form raisedsurfaces adapted to engage tissue at the native valve treatment site andanchor the personalized prosthetic valve.

The personalized prosthetic valve may further comprise a membranedisposed over the mesh. The membrane may be elastic and may conform tothe self-expanding mesh. The membrane may have an outer surface thatsubstantially matches the native valve treatment site shape in theexpanded configuration, and the membrane may form the central lumen. Themembrane may comprise a resilient polymer, and the polymer may beimpermeable to blood.

The personalized prosthetic valve may further comprise one or moreradiopaque markers coupled to the membrane or the self-expanding meshfor facilitating implantation of the personalized prosthetic valve atthe native valve treatment site. The prosthetic valve may also compriseone or more apertures extending through a sidewall of the personalizedprosthetic valve. The one or more apertures may be fluidly coupled withthe central lumen to allow blood flow or other fluids to flow betweenthe central lumen and the one or more apertures. The one or moreapertures may be configured to accommodate side branch vessels or otherbody passages such that the personalized prosthetic valve does notobstruct blood flow or fluid flow therethrough.

The native valve treatment site has a shape, and the lumen has a shapethat substantially matches the shape of the native valve treatment site.The lumen may not substantially alter blood flow path across thetreatment site. The lumen may have a cylindrical shape.

In still another aspect of the present invention, a personalizedprosthetic valve for implantation at a native valve of a patientcomprises a self-expanding membrane having a collapsed configuration andan expanded configuration. The collapsed configuration is adapted to bedelivered to the treatment site, and the expanded configuration isadapted to expand the personalized prosthesis into engagement with thetreatment site. The membrane in the expanded configuration ispersonalized to match the native valve, and the membrane has an outersurface that substantially matches the native valve shape and size inthe expanded configuration. The membrane forms a central lumenconfigured to allow blood or other body fluids to pass therethrough.

The prosthetic valve may further comprise a plurality of valve leafletscoupled to the self-expanding membrane that have an open configurationand a closed configuration. In the open configuration the blood or theother body fluids are free to pass through the personalized prostheticvalve. In the closed configuration the plurality of leaflets are closertoward one another than in the open configuration, and the blood or theother body fluids are prevented from flowing upstream through theprosthetic valve.

In another aspect of the present invention, a method for manufacturing apersonalized prosthetic valve comprises providing one or more images ofa native valve, creating a digital data set characterizing shape andsize of the native valve based on the one or more image, andtransforming the digital data set into machining instructions. Themethod also comprises forming a mandrel using the machininginstructions, wherein the mandrel has a shape that substantially matchesthe native valve, applying a mesh to the mandrel, and heat treating themesh while the mesh is disposed over the mandrel so that the mesh isbiased to return to a shape matching the shape of the native valvethereby forming the personalized prosthetic valve. The valve has acontracted configuration and an expanded configuration. The valve isadapted to be delivered to the native valve in the contractedconfiguration, and the valve is biased to return to the expandedconfiguration, which has a shape substantially matching the nativevalve.

Providing the one or more images may comprise providing one or moreimages obtained with computerized tomography (CT), magnetic resonanceimaging (MRI), x-ray, ultrasound, or angiography. Transforming thedigital data set into machining instructions may comprise transferringthe digital data set into a computer aided design or computer aidedmanufacturing (CAD/CAM) system. Forming the mandrel may comprisemachining a piece of metal. Forming the mandrel may comprise forming themandrel so as to be undersized relative to the native valve. Theundersized mandrel accommodates for thickness of the mesh.

Applying the mesh to the mandrel may comprise slidably disposing themesh over the mandrel. Applying the mesh to the mandrel may comprisewrapping a filament around the mandrel, or wrapping a preformed flatmesh around the mandrel. Heat treating the mesh may comprise heattreating a nitinol mesh.

The method may further comprise removing the mandrel from the mesh andrecovering the mesh. The method may also comprise forming at least oneside aperture in the personalized prosthetic valve that is configured toallow blood flow or other fluid flow therethrough. The method maycomprise forming a membrane over the mesh thereby forming a cover overthe personalized prosthetic valve. Forming the membrane may compriseattaching a polymer cover to the mesh or dip coating a polymer coverover the mesh.

The method may further comprise mounting the personalized prostheticvalve on a delivery catheter, cleaning the personalized prosthetic valveand delivery catheter, packaging the personalized prosthetic valve anddelivery catheter, and terminally sterilizing the personalizedprosthetic valve and delivery catheter. The method may compriserequesting verification that the shape of the personalized prostheticvalve is appropriate for implantation at the native valve beforeshipping the personalized prosthetic valve from a manufacturingfacility. Verification may be performed by a physician, and verificationmay be performed over the Internet. The method may comprise shipping thepersonalized prosthetic valve to a hospital.

The method may further comprise mounting the personalized prostheticvalve on a delivery catheter, placing the personalized prosthetic valveand the delivery catheter in packaging, sterilizing the personalizedprosthetic valve and the delivery catheter in the packaging, andrequesting verification that the personalized prosthetic valve isappropriate for implantation at the native valve site before opening thesterile packaging. The verification may be performed by a physician overthe internet. The method may further comprise removing the personalizedprosthetic valve from the mandrel so that a central lumen extendsthrough the personalized prosthetic valve. The native valve may be anaortic valve. Other valves are also contemplated such as mitral valves,tricuspid valves, pulmonary valves and other valves.

In still another aspect of the present invention, a method for treatinga damaged or diseased native valve a treatment site comprises providinga personalized prosthetic valve having a central lumen, an expandedconfiguration and a collapsed configuration. The valve is biased toexpand into the expanded configuration, and the valve is alsopersonalized to match shape of the treatment site. The central lumen isconfigured to allow blood flow or other body fluids to passtherethrough. The method also comprises advancing the personalizedprosthetic valve in the collapsed configuration to the treatment site,self-expanding the personalized prosthetic valve into the expandedconfiguration. The expanded configuration has a shape that substantiallymatches the shape of the treatment site such that the personalizedprosthetic valve expands substantially into engagement with the nativevalve at the treatment site. The method also comprises reducingretrograde blood flow across the native valve.

The personalized prosthetic valve may comprise a self-expanding wiremesh surrounded by a polymer cover, or the valve may comprise aself-expanding wire mesh, or the valve may comprise a resilient polymer.The treatment site has a shape and the lumen may have a shape thatsubstantially matches the shape of the treatment site. The lumen mayhave a cylindrical shape and the lumen may not substantially alter bloodflow path across the treatment site.

Advancing the personalized prosthetic valve may comprise advancing thevalve through a blood vessel. Radially expanding the prosthetic valvemay comprise retracting a sheath away from the personalized prostheticvalve, thereby allowing the personalized prosthetic valve to self-expandinto the expanded configuration. Reinforcing the tissue may compriseanchoring the personalized prosthetic valve to the tissue. The treatmentsite may comprise a native aortic valve, and reducing retrograde flowmay comprise directing blood flow through a plurality of valve leafletscoupled to the personalized prosthetic valve. The plurality of valveleaflets may have an open configuration and a closed configuration. Inthe closed configuration the plurality of valve leaflets may be adjacentone another to prevent the retrograde flow, and in the openconfiguration the plurality of valve leaflets may be disposed away fromone another and the blood flow may freely pass therethrough. Thetreatment site may comprise a native aortic valve.

Reinforcing the tissue may comprise anchoring the personalizedprosthetic valve in the native valve. Anchoring the personalizedprosthetic valve may comprise engaging barbs on the personalizedprosthetic valve with the tissue. The personalized prosthetic valve maycomprise one or more radiopaque markers, and the method may furthercomprise aligning the one or more radiopaque markers with one or moreanatomical features at the treatment site. The implantable prostheticvalve may comprise one or more apertures in a sidewall thereof, and themethod may comprise preventing obstruction of blood flow through the oneor more apertures in the sidewall.

These and other aspects and advantages of the invention are evident inthe description which follows and in the accompanying drawings.

INCORPORATION BY REFERENCE

All publications, patents, and patent applications mentioned in thisspecification are herein incorporated by reference to the same extent asif each individual publication, patent, or patent application wasspecifically and individually indicated to be incorporated by reference.

BRIEF DESCRIPTION OF THE DRAWINGS

The understanding of the features and advantages of the presentinvention will be obtained by reference to the following detaileddescription that sets forth illustrative embodiments, in which theprinciples of the invention are utilized, and the drawings of which:

FIG. 1 Shows the schematic view of the aorta showing the aortic valve;

FIG. 2 Shows the cross-sectional view of the aortic valve at sinotubularjunction;

FIG. 3 Illustrates the aortic valve in a close up view with the valveleaflets removed for convenience;

FIG. 4 Shows the flow diagram for the method of making the mesh for theaortic valve;

FIG. 5 Shows the mandrel matching the shape of the aortic valve;

FIG. 6 Shows the mesh conformally over the mandrel;

FIGS. 6A-6D illustrate exemplary methods of fabricating a personalprosthesis for the aortic valve;

FIG. 7 Illustrates the method of making the openings in the meshmatching the coronary ostia;

FIG. 8 Shows the mesh with coronary ostia on the mandrel;

FIG. 9 Shows the personalized finished mesh with alignment markers forthe aortic valve;

FIG. 10 Shows the personalized mesh deployed in the aortic valve cavity;

FIGS. 11A, 11B illustrate exemplary mesh patterns;

FIGS. 12A-12F illustrate exemplary mesh patterns;

FIG. 13 illustrates an exemplary embodiment of an end of a prosthesis;

FIG. 14 illustrates an exemplary mesh;

FIG. 15 illustrates another exemplary embodiment of a mesh pattern; and

FIG. 16 illustrates yet another exemplary embodiment of the mesh.

DETAILED DESCRIPTION OF THE INVENTION

The present invention will be described in relation to the deployment ofthe prosthesis in an aortic aneurysm. However, one of skill in the artwill appreciate that this is not intended to be limiting, and thedevices and methods disclosed herein may be used in other parts of thebody such as in the hollow anatomical structures including ducts,vessels, organs, or any other part of the body where there is a need toreinforce a lumen, channel, or other body space, or to anchor aprosthesis in those locations.

FIG. 1 shows the schematic view of the aorta from the aortic root to thethoracic portion of the descending aorta. The aortic valve is containedin the aortic root.

FIG. 2 shows the cross section of the aorta at the root across thesinotubular junction. The aortic valve has a sinus which anatomicallytypically has three pockets where the valve leaflets reside. Two of thepockets contain the ostia for the coronary arteries.

FIG. 3 shows the close-up view of the sinus pocket of the aortic valvewith the valve leaflets removed for convenience. It is situated justinferior to the sinotubular junction and joins the aorta to the leftventricle. It contains typically three bulbular pockets containing theleaflets. Two of the pockets contain the ostia for the coronaryarteries.

FIG. 4 shows a flow chart which illustrates an exemplary method offabricating a personalized prosthesis that can be used to be implantedin the aortic valve region or any other treatment region. The methodincludes obtaining one or more images 202 of the treatment region whichin this case is an aortic valve and surrounding blood vessel walls.These images may be obtained using computerized tomography (CT), x-ray,angiography, magnetic resonance imaging (MRI), ultrasound, or otherimaging techniques known to those of skill in the art. The images may bestored on any storage media such as a CD-ROM, flash memory stick, etc.,or the images may be stored in the cloud, on a remote server, or anyother convenient and secure location. The images may be transferred toany of these locations using the Internet. Once the images are stored,the images or the digital data representing the images may be input 204into a computer aided design/computer aided manufacturing (CAD/CAM)system. The CAD/CAM system then converts the images into a digital dataset that can then be translated into machining instructions which areprovided to a machining device such as a CNC lathe, mill, electricaldischarge machine (EDM), etc. and the machining instructions are used bythe machining device to machine 206 or otherwise form a mandrel or amold having a shape that substantially matches the shape and volume ofthe treatment region. Alternatively, the image data can be used toconstruct a three dimensional model of the treatment region using thetechniques such as 3-D printing. Thus the contours of the mandrel willmatch the contours of the treatment region, and the mandrel willsubstantially fill the volume of the treatment region, in this case, theaortic valve. The CAD/CAM system may be programmed to compensate for thethickness of materials that are applied to the mandrel later on, thusthe mandrel may be slightly smaller than the actual size of thetreatment region. Alternatively, the mandrel can be made of a sizeslightly larger so that the apposition of the mesh is more definitiveagainst the wall of the cavity where the mesh is intended to bedeployed. Although the mesh can be made smaller or largerproportionately in all dimensions, it would be more beneficial to makeit larger or smaller in the radial dimension only. In other embodiments,the mandrel shape will match the contours of the treatment regionwithout compensating for material thickness. In all cases, slightlysmaller, exactly the same, or slightly larger size of the resultingmandrel shape substantially matches the treatment region shape and size,and the mandrel will substantially fill the volume of the treatmentregion.

Once the mandrel is formed, it can be used as a master mold from which apersonalized prosthesis is fabricated. The personal prosthesis will thenhave a size and shape that substantially matches the treatment regionwhich allows the personal prosthesis to anchor itself at the treatmentregion and prevent perivalvular leaks or movement of the mesh. A wiremesh is either pre-made 208 or otherwise provided. The mesh ispreferably tubular and cylindrically shaped with both ends open so thatthe mesh may be slidably disposed over the mandrel like a sock, or inother embodiments the wire mesh may be wound 210 on the mandrel. Themesh and mandrel are then placed in a furnace, oven, salt bath, etc. toan elevated temperature for a desired time. The mesh and mandrel arethen removed and cooled using a prescribed cooling procedure such as aircooling, quenching in oil or water, etc. This heat treats 212 the wiremesh and the wire mesh takes a set to the shape of the mandrel. Heattreating of metals, in particular self-expanding metals is known in theart. The formed mesh is then removed from the mandrel. In thisembodiment, or any of the embodiments disclosed herein the wire mesh ispreferably self-expanding, and may be made from metals such assuperelastic nitinol, and thus the mesh will have an expandedconfiguration which matches the mandrel and hence also substantiallymatches the shape of the treatment region. When tension is applied tothe ends of the mesh, the mesh will collapse into a collapsedconfiguration which has a lower profile and is suitable for loading ontoa delivery catheter for endovascular delivery to the treatment region.The wire mesh in this or any of the embodiments described herein mayalso be a shape memory alloy such as nitinol such that placement of themesh in a patient's body heats the mesh above a transition temperatureand causes the mesh to radially expand outward.

Once the wire mesh has been heat treated to effect a shape, a fabric orpolymer coating may be applied 214 to the bulbular region of the wiremesh. This will allow for a seal against the inside wall of the valvethus preventing the perivalvular leaks. The coating may be Dacron®polyester, expanded polytetrafluorinated ethylene (ePTFE), silicone,polyurethane, or other materials known in the art. The coating may be asheet or tube of the material coupled to the mesh with adhesives,sutures, encapsulation, etc., or the mesh may be dip coated in order toapply the polymer to the mesh. The coating is preferably biocompatibleand impermeable to blood or other body fluids. It may also bebiodegradable and be made of materials such as polylactic acid (PLA) orpolyglycolic acid (PGA). The resulting wire mesh with polymer coatingforms a personalized implantable prosthesis having a shape that matchesthe treatment region and substantially fills the volume of the treatmentregion, in this case, the aortic valve. In other embodiments, the wiremesh remains uncoated and uncovered and forms the personalizedprosthesis. Over course of time, the wire mesh surface will getendothelialized and will become imbedded in the wall of the valve. Thepersonalized implantable prosthesis is then coupled to a delivery system215 such as a delivery catheter, and the system is then cleaned,packaged, and terminally sterilized 216 using manufacturing processesknown to those of skill in the art. For example, packaging may compriseplacing the prosthesis in a procedure tray and sealing the tray with aTyvek® lid, and terminally sterilizing the prosthesis may comprisegassing the prosthesis with ethylene oxide, autoclaving it with steam,or irradiating it with gamma or electron beam irradiation. Inalternative embodiments, the coating may be applied directly to themandrel without the mesh, thereby forming the prosthesis.

In some embodiments, the physician optionally may then confirm 218 thatthe resulting personal prosthesis is indeed the correct one for aparticular patient prior to shipping the prosthesis from the factory.The verification may be conducted visually over the Internet byverifying size, shape, or dimensions of the prosthesis. Once theverification is complete, the personal prosthesis may be shipped 219from the manufacturing facility to the doctor at a hospital,surgicenter, clinic or other place of business. Once received, thedoctor or an associate may then optionally re-verify 220 that theprosthesis is the correct size and shape for the patient prior toopening up the sterile package. If the prosthesis is incorrect, it maybe returned to the manufacturing facility. Verification may beaccomplished by scanning a bar code and/or using the Internet. Onceverification is complete, the personal prosthesis may be implanted 222in the appropriate patient. One of skill in the art will also appreciatethat appropriate patient privacy must be maintained during the entirepersonalized manufacturing process as required by the Health InsurancePortability and Accountability Act (HIPAA).

One desirable aspect of the present invention is to make the meshmatching the shape of the aortic valve and to have the anatomicallyaccurate openings in the said mesh for the coronary artery ostia. Thestructure and method of making the same is described below.

FIG. 5 shows the mandrel 310 made to match the shape and size of theaortic valve. The figure also shows the holes 312 and 314 in the mandrelmatching the locations of the coronary artery ostia. The locations ofthe apertures are accurately determined based on the image obtained,such as the CT scan and the like. The holes 312 and 314 are made bydrilling into the mandrel or may be made as tapped holes. The intendedfunction of the holes is to allow the attachment of pins or screws afterthe mesh has been mounted on the mandrel 310.

FIG. 6 shows the mandrel 310 with the mesh 316 disposed thereon. Thewire mesh 316 may be pre-fabricated into a tubular sock-like shape thatcan be easily placed over the mandrel as seen in FIG. 6A, or in otherembodiments, the wire mesh may be wound and formed over the mandrel. Instill other embodiments, such as seen in FIGS. 6B-6C, a flat preformedmesh 316 a (best seen in FIG. 6B) may be wrapped around the mandrel 310as seen in FIG. 6C. Once wrapped, the edges of the flat mesh may beaffixed to one another using methods known in the art such as welding,suturing, tying, bonding, soldering, etc. The mesh is thencircumferentially disposed around the mandrel as seen in FIG. 6D. Aribbon, wire, or other filament may be wrapped over the mesh to ensurethat it contacts the mandrel. FIG. 6 illustrates the wire mesh disposedover the mandrel in a manner described above.

Now referring to FIG. 7, the fenestrations (openings) in the mesh aremade using the pins 318 and 320. Pin 318 is inserted or screwed in tothe receiving hole 312 (FIG. 5) while displacing the intervening wires,such that the wires of the mesh are disposed around the pin 318 creatinga fenestration 322. Similarly pin 320 is placed in hole 314 (FIG. 5)creating the fenestration 324.

The mandrel and mesh along with the fenestrating pins are then heattreated as described previously so that the wire mesh takes a set to theshape of the mandrel. The resulting mesh-on-mandrel is shown in FIG. 8with the pins still in place. After heat treatment is completed, aportion of the mesh and mandrel may be dip coated with a polymer, or thepolymer or fabric cover 328 may be applied to the lower portion of themesh 316, as shown in FIG. 8, using methods known to those of skill inthe art. The polymer or fabric cover 328 is preferably impermeable toblood to prevent blood from flowing across the wall of the prosthesis.The covered portion of the mesh, when appositioned against thecorresponding inner wall of the valve, provides for the sealing of themesh so that the problem of perivalvular leak is mitigated.Alternatively, the entire mesh may be covered with a membrane coveringsuch as a dip-coated polymer or otherwise applied polymer or fabric. Thefenestrations 322 and 324 can be made by removing the membrane from thesite of said fenestrations by cutting, punching, dissolving, or othermeans known in the art. Alternatively, the coating 328 can be disposedon a portion or the whole mesh 316 after it has been removed from themandrel. The fenestrations 322 and 324 can then be created as describedabove.

FIG. 9 shows the finished mesh 316 which is disposed with thefenestrations 322 and 324 which match with the corresponding ostia ofthe coronary arteries. One or more location markers such as radiopaquemarkers 330, 332, and 334 markers are optionally attached to the polymeror fabric cover and/or to the wire mesh. The locations of the markersare selected based on the anatomical information obtained from thecorresponding image scan such as the CT scan. The said location may be acertain rib, vertebrae and the like. The markers 330, 332, and 334 areused for accurate alignment of the mesh in the aortic valve cavity. Allor portion of the mesh 316 may be dip coated with a polymer, or thepolymer or fabric cover 328 may be applied to the lower portion of themesh 316. Prosthetic valve leaflets may be coupled to the internalportion of the mesh thereby forming a prosthetic valve that permitsantegrade blood flow and prevents retrograde blood flow. The leaflets Lmay form a bicuspid or tricuspid valve, or other configurations ofleaflets may also be employed. The leaflets may be synthetic materialsuch as ePTFE, Dacron, or other materials may be used such aspericardial tissue.

FIG. 10 shows the mesh 316 positioned in the aortic valve cavity AV inanatomical alignment. The mesh has expanded into position such that theouter surface of the mesh substantially engages and conforms to theinner surface of the native valve and adjacent tissue such as the vesselwalls. Thus, the prosthetic valve is in engagement with the nativetissue and this helps to prevent perivalvular leakage around theprosthesis. Additionally, fenestrations 322, 324 are aligned with thenative coronary artery ostia, thus blood flow to the coronary artieriesremains substantially unobstructed. The prosthetic valve may bedelivered and aligned with the native valve anatomy and coronary arteryostia CAO by visualization of the radiopaque markers 330, 334.

The personalized prostheses described above preferably include a wiremesh that self-expands to the personalized shape. Various wire patternsmay be used to create the mesh. For example, FIG. 11A illustrates a mesh902 having one or more filaments 904 which are spirally wound and anoptional polymer or fabric cover 906 is applied to the mesh. Thispattern of forming the mesh is advantageous because there is no overlapof the filaments, and the spiral pattern helps the mesh to be collapsedinto a low profile for delivery. FIG. 11B shows the mesh 908 made of thefilaments 910 in the form of a braid and an optional polymer or fabriccover 910 is applied to the mesh.

FIGS. 12A-12F illustrate other exemplary mesh patterns. FIG. 12Aillustrates a mesh 1002 a having one or more filaments 1004 a thatinterweave with one another similar to traditional fencing wire orchicken wire, to form a single overlapping or twisted region 1006 a. Theoverlap region is preferably in every row and every column of the meshwhere the filaments meet. The overlapping region forms a protuberancewhich may be advantageous since the protuberance may help embed theprosthesis into the tissue at the treatment site thereby helping toanchor the prosthesis. Having a single overlap of the filaments helpsthe filaments move relative to one another thereby allowing theprosthesis to be easily collapsed which is desirable during loading ontoa delivery system and also helps to keep the profile of the prosthesisminimal. This is also advantageous since it allows the prostheses toexpand and collapse in concert with the pulsatile nature of the blood asit flows through the aorta or other vessel. However, in somecircumstances, the single overlapping or twisted region may not besecure enough to keep the mesh in its formed pattern or to provideadequate support to the aneurysm, especially when the prosthesis isunder tension or compression because the wires in the mesh may slip orslide relative to one another. The prosthesis undergoes tension andcompression during loading on a delivery system, during deployment, andafter implantation due to the pulsatile nature of blood flow.

FIG. 12B illustrates an alternative embodiment of a mesh pattern that ismore secure than the embodiment of FIG. 12A. Mesh 1002 b has one or morefilaments 1004 b that interweave with one another to form a doubleoverlapping or twisted region 1006 b. The overlap region is preferablyin every row and every column of the mesh where the filaments meet. Theoverlap region forms a protuberance similar to that in FIG. 12A and thusmay also be useful in anchoring the prosthesis. Having the doubleoverlapped or twisted region secures the filaments together more tightlyand thus helps prevents the filaments from slipping or sliding relativeto one another when the prosthesis is under tension or compression. Thusthe prosthesis retains its shape and provides more support than theembodiment in FIG. 12A. However, in some circumstances, the wires maystill slip or slide relative to one another, thus further securing ofthe filaments may be needed.

FIG. 12C illustrates still another embodiment of a mesh pattern whichhelps provide a stable mesh. The mesh 1002 c has one or more filaments1004 c that interweave with one another to form a triple overlapping ortwisted region 1006 c. The overlap region is preferably in every row andevery column of the mesh where the filaments meet. The overlap forms aprotuberance similar to those previously discussed and therefore may aidin anchoring of the prosthesis. Having the triple overlap or twistedregion secures the filaments together even more tightly than in theprevious embodiments and thus the filaments are further constrained fromslipping or sliding relative to one another when the prosthesis is undertension or compression. In some circumstances, having the triple overlapregion secures the filaments together tightly enough that they cannotmove at all relative to one another when the prosthesis is under tensionor compression. If the filaments cannot move at all relative to oneanother, this prevents the prosthesis from axially or radially expandingor contracting which interferes with its ability to be loaded in acollapsed configuration onto a delivery system, from expanding radiallyoutward upon deployment, or from expanding and contracting in concertwith the vessel wall due to pulsatile blood flow.

FIG. 12D illustrates a preferred hybrid embodiment of a mesh patternthat secures the filaments together securely so that the prosthesisholds its shape and provides good support during tension andcompression, and yet at the same time still allows some movement betweenthe filaments so that the prosthesis can expand and contract. Mesh 1002d has one or more filaments 1004 d that interweave with one another toform an alternating pattern of a triple overlap or twisted region 1006 dfollowed by a double overlap or twisted region 1008 d, followed byanother double or twisted overlap region 1008 d, and then the patternrepeats. The pattern repeats so that everywhere the filaments overlapwith one another, there is either a double or triple overlap or twistedregion. The overlap region forms a similar protuberance as previouslydescribed which may be useful for anchoring the prosthesis. This hybridweave has the advantages of both the double and triple overlap weavespreviously described. Thus, the triple overlap regions secure thefilaments together to minimize their movement relative to one anotherduring compression or tension and thus the prosthesis holds its shapeand provides good support, while at the same time the double overlapregions allow some movement of the filaments relative to one anotherthereby allowing the prosthesis to axially and radially expand andcontract during delivery, deployment, and after implantation. The weavepreferably minimizes or substantially eliminates axial expansion andcontraction while allowing radial expansion and contraction.

FIGS. 12E and 12F illustrates expansion and contraction of apersonalized prosthesis such as those described above using the weave ofFIG. 12D. Without being bound by any particular theory, it is believedthat the filaments will remain tightly engaged with one another when theprosthesis 1002 d is under tension such as while the heart is in systoleas seen in FIG. 12E and represented by arrows 1018 d. Here, thefilaments 1004 d remain tightly wound together in both the doubleoverlap region 1008 d as well as the triple overlap region 1006 d. Thegap 1012 d between adjacent filaments wound together in a region 1008 dmay be represented by distance S1 and the pitch 1010 d or spacingbetween adjacent columns of wound filaments may be represented bydistance P1 during systole. When the prosthesis is compressed such aswhen the heart is in diastole, as indicated by arrows 1020 d in FIG.12F, the pitch or spacing 1014 d between adjacent columns of woundfilaments generally decreases relative to the expanded configuration.Moreover, the gap 1016 d between adjacent filaments wound together in adouble overlap region 1008 d increases when the prosthesis is in theexpanded configuration thereby allowing the filaments to slide relativeto one another. The gap between adjacent filaments wound together in atriple overlap region remain twisted together and there is substantiallyno relaxation. Thus, when viewing the prosthesis laying on its side withits longitudinal axis horizontal, the triple-double-double-doublehorizontal weave pattern accommodates the motion of the aorta vesselwall caused by the pulsatile motion of the blood flowing through it. Ofcourse, one of skill in the art will appreciate that this particularpattern is not intended to be limiting. Other patterns may be usedincluding any combination or permutation of the single, double, triple,or more than three overlapping regions.

The filaments on the proximal and distal ends of the prosthesis may beterminated in any number of ways. FIG. 13 illustrates one exemplaryembodiment. The prosthesis 1602 has the triple-double-double-doubleweave pattern of FIGS. 12A-12F described above. The filaments mayterminate in an end region 1604 by twisting the filaments such that theyoverlap one another four times. One of skill in the art will appreciatethat this is not intended to be limiting and the number of overlappingregions may be one, two, three, four, five, six, or more. Alternatively,the filament ends may be tied in a knot to prevent the filaments fromunraveling. Additionally, the ends may remain extending axially outwardto help anchor the prosthesis in tissue by partially piercing thetissue, or the ends may be formed into curves, loops, or other shapes toprevent sharp ends from protruding and causing tissue trauma. Thisprevents the filaments from moving relative to one another.Additionally, the end region 1604 may then be bent slightly radiallyoutward 1606 to form a skirt or flanged region which flares outward andthus can embed into the vessel wall to help anchor the prosthesis.

In the embodiments of FIGS. 12A-12F, the weave pattern has beendescribed when the prosthesis is sitting on its side such that thelongitudinal axis of the prosthesis is generally horizontal. Thus, theweave pattern is generally parallel to the longitudinal axis, and thefilaments are weaved together in a horizontal pattern across theprosthesis and with a vertical orientation. In still other embodiments,the weave pattern of FIGS. 12A-12F may be rotated ninety degrees so thatthe filaments are weaved an orthogonal direction. FIG. 14 illustrates anexemplary embodiment of the weave pattern in FIG. 12A rotated ninetydegrees. The weave is illustrated with the prosthesis laying flat on itsside with its longitudinal axis generally horizontal. Thus, mesh 1202includes a plurality of filaments 1204 that are weaved together to forma single overlap or twisted region 1206. Other aspects of thisembodiment generally take the same form as in FIG. 12A. The otherembodiments described previously may also be weaved in a pattern thathas been rotated ninety degrees. Any of the mesh patterns describedherein may be formed into a round tubular member or the mesh may bewoven into a flat sheet and the ends may be joined together to form around tubular member. Additionally wires or filaments of differentdiameters may be combined with one other, or a single diameter may beused throughout a single mesh prosthesis in order to obtain desiredmechanical properties.

FIG. 15 illustrates still another pattern for the mesh 1102. Thispattern has one or more filaments 1104 woven into an undulating pattern.Adjacent rows of the undulating filaments are tied together with a wire,suture, or other tie 1106. Optionally, one or both ends of the tie 1106may be left uncut to form a barb 1108 that can also be used to helpanchor the prosthesis to tissue at the treatment site. Any of these wiremesh patterns with anchoring or without anchoring may be used in any ofthe embodiments described herein.

FIG. 16 illustrates yet another exemplary embodiment of a mesh. The mesh1302 includes one or more filaments 1304 which are formed into anundulating pattern having peaks and valleys. The peaks and valleys inone row of the mesh may overlap with the valleys and peaks of anadjacent row of the mesh. The overlapping portions may then be welded1306 together to keep the filaments coupled together. In alternativeembodiments, welds may be combined with any of the previous meshembodiments.

One objective behind the placement of the mesh against the wall of theaortic valve pocket is to apposition the mesh so that the perivalvularleak is eliminated. In addition, the secure apposition of the meshguards against any possible migration on the said mesh. After the meshis decisively appositioned against the aorta wall, an endothelial liningwill develop on the wire mesh over time, essentially imbedding the meshin the tissue covering the wall of the lumen. This process is welldocumented in animal models (for example, ref. ‘Time Course ofReendothelialization in a Normal Coronary Swine Model: Characterizationand Quantification’, A. Perez de Prado et al, Vetenary Pthology Online,Mar. 10, 2011;http://vet.sagepub.com/content/early/2011/03/10/0300985811400446)through the observations of the resident stents in the arteries, such ascoronary and carotid, of the vasculature. The endothelialization processtakes about two weeks or more, and within a few months, the wire meshwould be well imbedded in the wall of the lumen.

During the endothelialization process, the perivalvular leaks ormigration of the mesh may occur. Thus it would be beneficial if themesh, which is intended to be implanted in the aortic sinus pocket, isdesigned to be larger in size than the existing anatomical dimensions inthe radial dimension to accommodate the possibility of the aortic sinuspocket changing shape during the course of endothelialization andimbedding. A mesh larger than the actual implant site anatomy in radialdimension has two main advantages. First, the apposition of the meshagainst the wall of the aorta is more decisive at the time ofdeployment. Secondly, the larger mesh continues to remain firmlyappositioned against the aortic lumen wall during the endothelializationprocess when the adjacent tissue could possibly grow larger.

The mesh needs to be larger only in the radial dimension, and not in theaxial dimension (i.e. along the length of the aorta). The mesh can bedesigned and built to be larger by 1% to 15%, preferably 5% to 10%, thanthe then existing implantation site anatomy size in the radialdimension.

In any of the embodiments described herein, the filament may be a wirehaving any cross-section such as round, square, rectangular, etc. andthe size of the wire may be adjusted in order to various properties ofthe prosthesis such as its profile in the collapsed configuration, itsstiffness and strength, and other properties. In preferred embodiments,a round nitinol wire is used having a diameter of 0.004 inches to 0.008inches.

Additionally, any of the prostheses may carry a therapeutic agent suchas an antithrombotic agent, antibiotic, etc. for localized andcontrolled elution at the treatment site. One of skill in the art willalso appreciate that the prosthesis described herein preferably has amesh with a polymer or fabric cover disposed thereover, but theprosthesis could be a mesh only to support the damaged or diseasedtissue, or the prosthesis could be the polymer or fabric cover only.Thus, the fabrication methods and delivery methods described hereinapply to either embodiment of prosthesis.

While preferred embodiments of the present invention have been shown anddescribed herein, it will be obvious to those skilled in the art thatsuch embodiments are provided by way of example only. Numerousvariations, changes, and substitutions will now occur to those skilledin the art without departing from the invention. For example, thedevices are described with respect to a prosthetic aortic valve, howeverone of skill in the art that the devices and methods may also be appliedto any heart valve such as the mitral valve, the tricuspid valve or thepulmonary valve. Additionally, the techniques described herein may beapplied to any other valve in the body. It should be understood thatvarious alternatives to the embodiments of the invention describedherein may be employed in practicing the invention. It is intended thatthe following claims define the scope of the invention and that methodsand structures within the scope of these claims and their equivalents becovered thereby.

What is claimed is:
 1. A personalized prosthetic valve for implantationat a native valve treatment site, said personalized prosthetic valvecomprising: a self-expanding mesh having a collapsed configuration andan expanded configuration, the collapsed configuration adapted to bedelivered to the native valve treatment site, and the expandedconfiguration adapted to expand the valve into engagement with thetreatment site, wherein the mesh in the expanded configuration ispersonalized to match the treatment site, wherein the mesh has an outersurface that substantially matches the native valve treatment site shapeand size in the expanded configuration, and wherein the self-expandingmesh forms a central lumen configured to allow blood or other bodyfluids to pass therethrough, and wherein the valve further comprises aplurality of valve leaflets coupled to the self-expanding mesh andhaving an open configuration and a closed configuration, wherein in theopen configuration the blood or the other body fluids are free to passthrough the valve, and wherein in the closed configuration the pluralityof leaflets are closer toward one another than in the openconfiguration, and the blood or the other body fluids are prevented fromflowing upstream through the prosthetic valve.
 2. The personalizedprosthetic valve of claim 1, wherein the self-expanding mesh comprises anitinol mesh.
 3. The personalized prosthetic valve of claim 1, whereinthe self-expanding mesh comprises one or more filaments in a helicalpattern.
 4. The personalized prosthetic valve of claim 1, wherein theself-expanding mesh comprises one or more filaments woven together toform overlapping regions with the one or more filaments overlapping oneanother at least once.
 5. The personalized prosthetic valve of claim 1,wherein the self-expanding mesh comprises one or more filaments woventogether to form a first overlapping region and a second overlappingregion, wherein in the first overlapping region the filaments overlapwith one another a first number of times, and wherein in the secondoverlapping region the filaments overlap with one another a secondnumber of times different than the first number of times.
 6. Thepersonalized prosthetic valve of claim 1, wherein the self-expandingmesh comprises barbs or hooks adapted to engage tissue at the treatmentsite and anchor the personalized prosthesis.
 7. The personalizedprosthetic valve of claim 1, wherein the self-expanding mesh comprises aplurality of overlapping filaments forming overlapping regions, andwherein the overlapping regions form raised surfaces adapted to engagetissue at the native valve treatment site and anchor the personalizedprosthetic valve.
 8. The personalized prosthetic valve of claim 1,further comprising a membrane disposed over the mesh, wherein themembrane is elastic and conforms to the self-expanding mesh, and whereinthe membrane has an outer surface that substantially matches the nativevalve treatment site shape in the expanded configuration, and whereinthe membrane forms the central lumen.
 9. The personalized prostheticvalve of claim 8, wherein the membrane comprises a resilient polymer.10. The personalized prosthetic valve of claim 8, wherein the polymer isimpermeable to blood.
 11. The personalized prosthetic valve of claim 1,further comprising one or more radiopaque markers coupled to themembrane or the self-expanding mesh for facilitating implantation of thepersonalized prosthetic valve at the native valve treatment site. 12.The personalized prosthetic valve of claim 1, further comprising one ormore apertures extending through a sidewall of the personalizedprosthetic valve, the one or more apertures fluidly coupled with thecentral lumen to allow blood flow or other fluids to flow between thecentral lumen and the one or more apertures, the one or more aperturesconfigured to accommodate side branch vessels or other body passagessuch that the personalized prosthetic valve does not obstruct blood flowor fluid flow therethrough.
 13. The personalized prosthetic valve ofclaim 1, wherein the native valve treatment site has a shape, andwherein the lumen has a shape substantially matching the shape of thenative valve treatment site.
 14. The personalized prosthetic valve ofclaim 1, wherein the lumen does not substantially alter blood flow pathacross the treatment site.
 15. The personalized prosthetic valve ofclaim 1, wherein the lumen has a cylindrical shape.
 16. A personalizedprosthetic valve for implantation at a native valve of a patient, saidpersonalized prosthetic valve comprising: a self-expanding membranehaving a collapsed configuration and an expanded configuration, thecollapsed configuration adapted to be delivered to the treatment site,and the expanded configuration adapted to expand the personalizedprosthesis into engagement with the treatment site, wherein the membranein the expanded configuration is personalized to match the native valve,and wherein the membrane has an outer surface that substantially matchesthe native valve shape and size in the expanded configuration, andwherein the membrane forms a central lumen configured to allow blood orother body fluids to pass therethrough.
 17. The personalized prostheticvalve of claim 16, further comprising a plurality of valve leafletscoupled to the self-expanding membrane and having an open configurationand a closed configuration, wherein in the open configuration the bloodor the other body fluids are free to pass through the personalizedprosthetic valve, and wherein in the closed configuration the pluralityof leaflets are closer toward one another than in the openconfiguration, and the blood or the other body fluids are prevented fromflowing upstream through the prosthetic valve.
 18. A method formanufacturing a personalized prosthetic valve, said method comprising:providing one or more images of a native valve; creating a digital dataset characterizing shape and size of the native valve based on the oneor more images; transforming the digital data set into machininginstructions; forming a mandrel using the machining instructions,wherein the mandrel has a shape that substantially matches the nativevalve; applying a mesh to the mandrel; heat treating the mesh while themesh is disposed over the mandrel so that the mesh is biased to returnto a shape matching the shape of the native valve thereby forming thepersonalized prosthetic valve, the valve having a contractedconfiguration and an expanded configuration, wherein the valve isadapted to be delivered to the native valve in the contractedconfiguration, and wherein the valve is biased to return to the expandedconfiguration, the expanded configuration having a shape substantiallymatching the native valve.
 19. The method of claim 18, wherein providingthe one or more images comprises providing one or more images obtainedwith computerized tomography (CT), magnetic resonance imaging (MRI),x-ray, ultrasound, or angiography.
 20. The method of claim 18, whereintransforming the digital data set into machining instructions comprisestransferring the digital data set into a computer aided design orcomputer aided manufacturing (CAD/CAM) system.
 21. The method of claim18, wherein forming the mandrel comprises machining a piece of metal.22. The method of claim 18, wherein forming the mandrel comprisesforming the mandrel so as to be undersized relative to the native valve,the undersized mandrel accommodating for thickness of the mesh.
 23. Themethod of claim 18, wherein applying the mesh to the mandrel comprisesslidably disposing the mesh over the mandrel.
 24. The method of claim18, wherein applying the mesh to the mandrel comprises wrapping afilament around the mandrel.
 25. The method of claim 18, whereinapplying the mesh to the mandrel comprises wrapping a preformed flatmesh therearound.
 26. The method of claim 18, wherein heat treating themesh comprises heat treating a nitinol mesh.
 27. The method of claim 18,further comprising removing the mandrel from the mesh and recovering themesh.
 28. The method of claim 18, further comprising forming at leastone side aperture in the personalized prosthetic valve, the at least oneside aperture configured to allow blood flow or other fluid flowtherethrough.
 29. The method of claim 18, further comprising forming amembrane over the mesh thereby forming a cover over the personalizedprosthetic valve.
 30. The method of claim 29, wherein forming themembrane comprises attaching a polymer cover to the mesh.
 31. The methodof claim 29, wherein forming the membrane comprises dip coating apolymer cover over the mesh.
 32. The method of claim 18, furthercomprising: mounting the personalized prosthetic valve on a deliverycatheter; cleaning the personalized prosthetic valve and deliverycatheter; packaging the personalized prosthetic valve and deliverycatheter; and terminally sterilizing the personalized prosthetic valveand delivery catheter.
 33. The method of claim 18, further comprisingrequesting verification that the shape of the personalized prostheticvalve is appropriate for implantation at the native valve beforeshipping the personalized prosthetic valve from a manufacturingfacility.
 34. The method of claim 33, wherein the verification isperformed by a physician.
 35. The method of claim 33, wherein theverification is performed over the Internet.
 36. The method of claim 18,further comprising shipping the personalized prosthetic valve to ahospital.
 37. The method of claim 18, further comprising: mounting thepersonalized prosthetic valve on a delivery catheter; placing thepersonalized prosthetic valve and the delivery catheter in packaging;sterilizing the personalized prosthetic valve and the delivery catheterin the packaging; and requesting verification that the personalizedprosthetic valve is appropriate for implantation at the native valvesite before opening the sterile packaging.
 38. The method of claim 37,wherein the verification is performed by a physician.
 39. The method ofclaim 37, wherein the verification is performed over the Internet. 40.The method of claim 18, further comprising removing the personalizedprosthetic valve from the mandrel so that a central lumen extendsthrough the personalized prosthetic valve.
 41. The method of claim 18,wherein the native valve is an aortic valve.
 42. A method for treating adamaged or diseased native valve a treatment site, said methodcomprising: providing a personalized prosthetic valve having a centrallumen, an expanded configuration and a collapsed configuration, andwherein the personalized prosthetic valve is biased to expand into theexpanded configuration, and wherein the personalized prosthetic valve ispersonalized to match shape of the treatment site, and wherein thecentral lumen is configured to allow blood flow or other body fluids topass therethrough; advancing the personalized prosthetic valve in thecollapsed configuration to the treatment site; self-expanding thepersonalized prosthetic valve into the expanded configuration, whereinin the expanded configuration the personalized prosthetic valve has ashape that substantially matches the shape of the treatment site suchthat the personalized prosthetic valve expands substantially intoengagement with the native valve at the treatment site; and reducingretrograde blood flow across the native valve.
 43. The method of claim42, wherein the personalized prosthetic valve comprises a self-expandingwire mesh surrounded by a polymer cover.
 44. The method of claim 42,wherein the personalized prosthetic valve comprises a self-expandingwire mesh.
 45. The method of claim 42, wherein the personalizedprosthetic valve comprises a resilient polymer.
 46. The method of claim42, wherein the treatment site has a shape, and wherein the lumen has ashape substantially matching the shape of the treatment site.
 47. Themethod of claim 42, wherein the lumen has a cylindrical shape.
 48. Themethod of claim 42, wherein the lumen does not substantially alter bloodflow path across the treatment site.
 49. The method of claim 42, whereinadvancing the personalized prosthetic valve comprises advancing thepersonalized prosthetic valve through a blood vessel.
 50. The method ofclaim 42 wherein radially expanding the personalized prosthetic valvecomprises retracting a sheath away from the personalized prostheticvalve, thereby allowing the personalized prosthetic valve to self-expandinto the expanded configuration.
 51. The method of claim 42, whereinreinforcing the tissue comprises anchoring the personalized prostheticvalve to the tissue.
 52. The method of claim 42, wherein the treatmentsite comprises a native aortic valve, and reducing retrograde flowcomprises directing blood flow through a plurality of valve leafletscoupled to the personalized prosthetic valve, wherein the plurality ofvalve leaflets have an open configuration and a closed configuration,wherein in the closed configuration the plurality of valve leaflets areadjacent one another to prevent the retrograde flow, and wherein in theopen configuration the plurality of valve leaflets are disposed awayfrom one another and the blood flow freely passes therethrough.
 53. Themethod of claim 42, wherein the treatment site comprises a native aorticvalve.
 54. The method of claim 42, wherein reinforcing the tissuecomprises anchoring the personalized prosthetic valve in the nativevalve.
 55. The method of claim 54, wherein anchoring the personalizedprosthetic valve comprises engaging barbs on the personalized prostheticvalve with the tissue.
 56. The method of claim 42, wherein thepersonalized prosthetic valve comprises one or more radiopaque markers,the method further comprising aligning the one or more radiopaquemarkers with one or more anatomical features at the treatment site. 57.The method of claim 42, wherein the personalized prosthetic valvecomprises one or more apertures in a sidewall thereof, the methodfurther comprising preventing obstruction of blood flow through the oneor more apertures in the sidewall.